G6PD Deficiency / Uric Acid / Thalassemia

Hi Andy,

Quick question for you mate;
After all the issues I went through whilst on Allopurinol for my high uric  (haemoglobin drop etc. which haematologists are not convinced is due to Allopurinol) we have moved to Febuxostat.
Now I have been increasing my dose very slowly and I have noticed a very slight drop in haemoglobin whilst being on it.
Now its not really enough to justify stopping Febuxostat just yet (down from 7.2 to 6.6) - what do you think..?

On another note, I took a G6PD test the other day to see if this may be the cause of all my dilemas and the result has come back as [27.1 U/g Hb]  The 'normal ramge' is [5.6 - 11.2 U/g Hb].
Is the result being on the high side a better result then the low side?  For that matter, does the test indicate I have a G6PD problem..?

Thanks mate - your a top man.

I don't really like seeing thals use drugs that contain sulfur, due to the potential for hemolytic anemia. I would say watch your Hb closely.

A low G6PD level would make for more fragile RBC's but I don't know if it would be relevant, as the fragility of RBC's in thalassemia is not related to G6PD deficiency.

Hi @Andy,

Honestly mate, you are a top man.

I've got my next blood test scheduled for next week and if I notice any drop I will immediately stop the Febuxostat.

I'm just counting the days to get onto the Luspatercept trial should I qualify.

Is there anything you know I can do to reduce my uric acid levels (Diet alone is just not going to cut it)..?
It stands at around 585ummol with no treatment but obviously in the long term I will end up with even worse gout if I don't treat it.
There is another drug called Probenecid which helps excrete more uric acid through the kidneys but I believe it also contains sulfur but what other choices do I have..?
I'm just worried that all this uric acid is actually protecting my red cells from Oxidative damage..?

Assuming Luspatercept works could we see a fall in the uric acid due to the massive red cell turnover, have there been any observations on this?
By the way, I believe Vitamin B1 also has sulfur through Thiamine, I recently started a Vitamin B complex (3 weeks ago), could this also be a reason for the hgb drop?

Thanks Andy.

p.s. any plans to visit UK..?

Sorry for all the questions buddy..

Luspatercept greatly reduced ineffective erythropoiesis in the bone marrow, which greatly reduces the number of defective RBC's produced. This should cause a decrease in bilirubin and uric acid, but I don't know if this data was released from Phase 2. Phase 3 will results should give a better understanding about improvements in various areas of health.

I think with the gout meds, you just have to observe the effects and see if any work better for you. I just hope that this problem in thal minor will be recognized and treated as an overactive bone marrow problem and not a dietary one. Eliminating ineffective erythropoiesis would ameliorate almost all the problems of thal minor. I can see that Luspatercept has potential here, but will doctors see it?

@Andy

Hi mate, thanks for that fantastic reply. It's really given me hope for the future. The few gout attacks I've had over the years have been debilitating. I've started the febuxostat and I have noticed something very interesting. It seems as if every time I lower my uric acid to safer levels my haemoglobin seems to drop in linear (the lower the uric acid the lower the haemoglobin). As we know Uric Acid is a very powerful anti-oxidant which seems to point us to an interesting discussion that "potentially" reducing uric acid levels in thalassemics reduces the anti-oxidant benefit provided by it which could cause these fragile red cells to breakdown easier.

Now I have yet to confirm my theory as I have noticed this primarily with Allopurinol. Now that I have started febuxostat I will be monitoring carefully to see if the results are similar. If they are this leads us to 3 possible outcomes:

A) uric acid is actually potentially protecting red cells thus haemoglobin drops when uric acid drops
B) something in these 2 drugs (sulfar or otherwise) causes red cell turnover after being exposed to it
C) my body is reacting negatively to both allopurinol and febuxostat causing this haemoglobin drop

A possible test that can be conducted is to have an intense anti-oxidant regime using but not limited to mixed tocopherols whilst taking allopurinol or febuxostat and seeing if one can compensate for potential oxidative damage originating from the lower uric acid levels. I will attempt this after my next blood test so we have a baseline. It'll be very interesting to see the results if your interested.

If Luspatercept does correct the erythropoietis as you say we should see lower uric acid levels and lower bilirubin levels, we should also see lower pulse rates and reduced heart load.

What I forgot to mention to you is I have non transfusion dependant thalasemmia intermedia and not minor, would I still see the same benefits from Luspatercept (lower uric acid and bilirubin)..?

Finally do we have any phase 3 results from non-transfusion dependant thalassemia intermediates?

Once again many many thanks.

Being intermedia, you will probably have a good chance of a doctor prescribing Luspatercept once it is approved. The higher hemoglobin level would reduce or eliminate so many of the problems of thal, such as the stress on the heart caused by the low Hb and the heart's attempt to compensate.

There are no results released from the phase 3 trials. I have heard anecdotal reports and some patients are doing extremely well.

Thanks Andy mate.

I have my next haematologist appointment in a few days alongside a blood test to see how Febuxostat is doing. Once I get these results I'll update you buddy.

What I forgot to ask was if you know of any other new treatments for thalasemmia intermedia?
Maybe Lentiglobin? Foxo3 (something about anti oxidant damage)? 

I'm just worried that Luspatercept won't work if I get it 

Lentiglobin is bluebird's gene therapy, which has already cured intermedia thals, and has shown improved output as time has passed in at least one beta zero patient. It's a matter of time until they seek approval. I'd like to learn if they are going to seek approval for using it with non-beta zero thals or wait until after they run the new beta zero trial. That would slow it down by several years, if they do.
The Foxo3 research is fairly new, but is one of many different approaches to thalassemia treatment currently being developed.